No description available.

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The coagulation and fibrinolytic systems are linked by the thrombin-thrombomodulin complex which regulates each system through activation of protein C and TAFI, respectively. We have used novel assays and techniques to study the enzymology and biochemistry of TAFI and TAFIa, to measure TAFI activation in hemophilia A and protein C deficiency and to determine if enhancing TAFI activation can improve hemostasis in hemophilic plasma and whole blood. We show that TAFIa not TAFI attenuates fibrinolysis in vitro and this is supported by a relatively high catalytic efficiency (16.41μM-1s-1) of plasminogen binding site removal from fibrin degradation products (FDPs) by TAFIa. Since the catalytic efficiency of TAFIa in removing these sites is ~60-fold higher than that for inflammatory mediators such as bradykinin it is likely that FDPs are a physiological substrate of TAFIa. The high catalytic efficiency is primarily a result of a low Km which can be explained by a novel mechanism where TAFIa forms a binary complex with plasminogen and is recruited to the surface of FDPs. The low Km also suggests that TAFIa would effectively cleave lysines from FDPs during the early stages of fibrinolysis (i.e. at low concentrations of FDPs). Since individuals with hemophilia suffer from premature fibrinolysis as a result of insufficient TAFI activation we quantified TAFI activation in whole blood from hemophilic subjects. Both the rate of activation and the area under the TAFI activation time course (termed TAFIa potential) was determined to be reduced in hemophilia A and the TAFIa potential was significantly and inversely correlated with the clinical bleeding iii phenotype. Using a novel therapeutic strategy, we used soluble thrombomodulin to increase TAFI activation which improved the clot lysis time in factor VIII deficient human plasma and hemophilic dog plasma as well as hemophilic dog blood. Finally, we briefly show in a biochemical case study that TAFI activation is enhanced in protein C deficiency and when afflicted individuals are placed on Warfarin anticoagulant therapy, TAFI activation is reduced. Since TAFIa stabilizes blood clots, this suggests that reducing TAFI activation or inhibiting TAFIa may help restore blood flow in vessels with pathological thrombosis. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2010-09-23 10:12:18.892

The response of soil arylsulfatase enzymes to natural and artificial substrates was evaluated. An immobilized arylsulfatase reactor was used to hydrolyse ester sulfate compounds in two soils with different morphological properties and management schemes. Hydrolysable ester sulfates cleaved by the immobilized arylsulfatase reactor constituted 35 to 55% of the HI-reducible S in these soils. Naturally occurring low molecular weight (LMW) ester sulfate compounds were found to accumulate in soil and persist during storage. These compounds were examined as the naturally occurring substrate for soil arylsulfatase enzymes. / Arylsulfatase activity was evaluated using artificial (p-nitrophenol sulfate) and natural (LMW ester sulfates) substrates. The response of arylsulfatase activity in soil and humic-arylsulfatase complexes to p-nitrophenol sulfate did not reflect the ability of these complexes to hydrolyse natural soil substrates. / A preliminary experiment was conducted to examine arylsulfatase activity and soil sulfur in relation to sulfur in plant tissue and grain from wheat. Tissue sulfur was more strongly associated with soil sulfur than wheat grain.

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Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references (p. 144-163).

Thesis (Ph.D.) - University of St Andrews, January 2010.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 101-107).